Article(id=1320882230323429407, tenantId=1146029695717560320, journalId=1260987677001138203, issueId=1320882022160126288, articleNumber=null, orderNo=null, doi=10.13386/j.issn1002-0306.2024120375, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1735488000000, receivedDateStr=2024-12-30, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1792852464514, onlineDateStr=2026-10-24, pubDate=1767196800000, pubDateStr=2026-01-01, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792852464514, onlineIssueDateStr=2026-10-24, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792852464514, creator=13701087609, updateTime=1792852464514, updator=13701087609, issue=Issue{id=1320882022160126288, tenantId=1146029695717560320, journalId=1260987677001138203, year='2026', volume='47', issue='1', pageStart='1', pageEnd='498', issueExtLink='null', onlineDate='null', pubDate='1767196800000', pubDateStr='2026-01-01', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792852414884, creator='13701087609', updateTime=1792852414884, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=420, endPage=432, ext={EN=ArticleExt(id=1320882232001151008, articleId=1320882230323429407, tenantId=1146029695717560320, journalId=1260987677001138203, language=EN, title=Effect and Approach of Combined Prebiotics in Alleviating Constipation, columnId=1261343846965830077, journalTitle=Science and Technology of Food Industry, columnName=Nutrition and Healthcare, runingTitle=null, highlight=null, articleAbstract=

Objective: Constipation is a common functional gastrointestinal disorder, necessitating sustainable and side-effect-free relief methods. Methods: This study investigated the efficacy of combined prebiotics in a loperamide-induced constipation mouse model. Further assessments included gut microbiota composition, fecal short-chain fatty acid levels, intestinal barrier-related markers, colonic tissue damage, and gastrointestinal regulatory neurotransmitters. Results: Combined prebiotics alleviated constipation by downregulating the abundance of harmful bacteria (Bilophila, Anaerovorax) and upregulating the abundance of beneficial bacteria (Ileibacterium, Bifidobacterium), thereby increasing excitatory gastrointestinal neurotransmitters (upregulating gastrin and substance P), improving the intestinal barrier (upregulating MUC2, Occludin, and SCF mRNA expression while downregulating AQP3 mRNA relative expression), repairing colonic tissue damage, and elevating fecal acetate and butyrate levels. These changes led to a 27% reduction in time to first black stool excretion and 46% increase in fecal water content compared to the model group. When combined with prune juice, the prebiotics formulation further enhanced the abundance of beneficial bacteria (Odoribacter, Faecalibaculum, Defluviitaleaceae_UCG-011), increased gastrin and motilin levels, decreased calcitonin gene-related peptide, upregulated MUC2 mRNA, elevated fecal acetate and butyrate, improved small intestinal propulsion rate (by 47% compared to the model group), and increased fecal output within 5 hours (by 132% compared to the model group), demonstrating superior constipation relief. Conclusion: The study demonstrates that the combined prebiotics (containing 3 g xylooligosaccharides, 3 g stachyose, and 8 g galactooligosaccharides per 100 mL) effectively relieve constipation. Prebiotics combined with prune juice further enhancing efficacy through improved intestinal motility and microbiota modulation. These findings support the development of multi-component prebiotic formulations and reveal prune juice's potential to amplify prebiotic effects, providing a scientific basis for novel constipation management strategies.

, authors=Huahao CAI1, 2, Yunzhu LIU3, Shengnan ZHU1, Rong WANG1, 2, Qianqian LI1, 2, Li ZHANG1, 2, Linlin WANG1, 2, *, Shumao CUI1, 2, authorsList=Huahao CAI, Yunzhu LIU, Shengnan ZHU, Rong WANG, Qianqian LI, Li ZHANG, Linlin WANG, Shumao CUI, authorCompany=null, correspAuthors=Linlin WANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright © 2026 Science and Technology of Food Industry. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1320882234291241013, articleId=1320882230323429407, tenantId=1146029695717560320, journalId=1260987677001138203, language=CN, title=复配益生元缓解便秘效果和途径探究, columnId=1261343850979779009, journalTitle=食品工业科技, columnName=营养与保健, runingTitle=null, highlight=null, articleAbstract=

目的:便秘是一种常见的功能性胃肠疾病,需要可持续且无副作用的缓解手段。方法:本研究采用洛哌丁胺诱导小鼠便秘模型,评估了复配益生元对便秘的缓解作用。研究首先考察了复配益生元对便秘表观指标的影响,后续进一步对便秘相关胃肠调节递质、肠道屏障系统、结肠组织损伤情况、粪便内短链脂肪酸含量和肠道菌群进行了检测。结果:复配益生元可以通过下调有害菌Bilophila、Anaerovorax的相对丰度,上调有益菌Ileibacterium、Bifidobacterium的相对丰度,从而上调结肠内兴奋性胃肠调节递质含量(胃泌素和P物质),改善肠道屏障系统(上调粘蛋白2、闭锁蛋白、干细胞因子表达量,下调水通道蛋白3 mRNA相对表达量),改善结肠组织损伤,上调粪便中乙酸、丁酸含量,最终下调排首粒黑便时间(相比模型组缩短了27%),增加粪便含水量(相比模型组增加了46%),有效缓解便秘。而复配益生元与西梅汁复配后可以进一步上调有益菌Odoribacter、Faecalibaculum、Defluviitaleaceae_UCG-011的相对丰度,进一步上调结肠内胃泌素、胃动素含量,下调结肠内降钙素基因相关肽含量,上调粘蛋白2 mRNA相对表达量,上调粪便中乙酸、丁酸含量,增加小肠推进率(相比模型组增加了47%)和5 h内排便量(相比模型组增加了132%),从而更有效地缓解便秘。结论:复配益生元(每100 mL中主要含有低聚木糖3 g、水苏糖3 g、低聚半乳糖8 g)可缓解便秘,益生元与西梅汁复配后可以通过增强小肠推进率和提高菌群调节能力进而更有效地缓解便秘。本研究发现了西梅汁可以增强益生元缓解便秘的功效,为多种类低剂量益生元配方的开发提供了数据支持,为后续开发新型便秘缓解策略提供了科学依据。

, authors=蔡华昊1, 2, 刘运柱3, 朱胜男1, 王榕1, 2, 李乾乾1, 2, 张莉1, 2, 王琳琳1, 2, *, 崔树茂1, 2, authorsList=蔡华昊, 刘运柱, 朱胜男, 王榕, 李乾乾, 张莉, 王琳琳, 崔树茂, authorCompany=null, correspAuthors=王琳琳, authorNote=

蔡华昊(1998−),男,硕士,研究方向:益生菌与健康,E-mail:

, correspAuthorsNote=
王琳琳(1985−),女,博士,副研究员,研究方向:益生菌与健康,E-mail:。
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The Journal of Nutrition, 2023, 153(11): 3193−3206., articleTitle=null, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1320882234526122038, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, xref=1, ext=[AuthorCompanyExt(id=1320882234534510647, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, companyId=1320882234526122038, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1School of Food Science and Technology, Jiangnan University, Wuxi 214122, China), AuthorCompanyExt(id=1320882234542899256, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, companyId=1320882234526122038, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1江南大学食品学院,江苏无锡 214122)]), AuthorCompany(id=1320882234622591033, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, xref=2, ext=[AuthorCompanyExt(id=1320882234635173946, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, companyId=1320882234622591033, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Wuxi Institute for Specialized Nutrition and Health, Wuxi 214112, China), AuthorCompanyExt(id=1320882234639368251, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, companyId=1320882234622591033, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2无锡特殊食品与营养健康研究院有限公司,江苏无锡 214112)]), AuthorCompany(id=1320882236291924029, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, xref=3, ext=[AuthorCompanyExt(id=1320882236300312638, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, companyId=1320882236291924029, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3Shandong Yingbeijian Health Food Co., Ltd., Jinan 251414, China), AuthorCompanyExt(id=1320882236308701247, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, companyId=1320882236291924029, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3山东英贝健健康食品有限公司,山东济南 251414)])], figs=[ArticleFig(id=1320882241023099003, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.1, caption=Animal experiment process, figureFileSmall=Sgm7QX6bXuW98o9Sd0XEpA==, figureFileBig=GujDxrJVzneNT5OGPeXA9Q==, tableContent=null), ArticleFig(id=1320882241094402172, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图1, caption=动物实验流程, figureFileSmall=Sgm7QX6bXuW98o9Sd0XEpA==, figureFileBig=GujDxrJVzneNT5OGPeXA9Q==, tableContent=null), ArticleFig(id=1320882241266368637, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.2, caption=Effect of prebiotics and prune juice on constipation related indicators in mice, figureFileSmall=Fsvr1mXnfRpEIoU2tR8jDw==, figureFileBig=f3R1TX0it1hKdn7qnYRy1w==, tableContent=null), ArticleFig(id=1320882241341866110, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图2, caption=复配益生元和西梅汁对小鼠便秘相关指标的影响

注:#表示模型组与溶剂对照组对比有显著性差异,#:P<0.05,##:P<0.01,###:P<0.001;*表示干预组与模型组对比有显著性差异,*:P<0.05,**:P<0.01,***:P<0.001;ns表示差异不显著;图3~图4、图6~图7、图9同。

, figureFileSmall=Fsvr1mXnfRpEIoU2tR8jDw==, figureFileBig=f3R1TX0it1hKdn7qnYRy1w==, tableContent=null), ArticleFig(id=1320882241408974975, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.3, caption=Effect of prebiotics and prune juice on gastrointestinal regulatory neurotransmitters in mice, figureFileSmall=evKq+eDp9BDzRHEWBIQXkw==, figureFileBig=nRi8Ko5Ohk80zYxMTdKWnA==, tableContent=null), ArticleFig(id=1320882241497055360, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图3, caption=复配益生元和西梅汁对小鼠便秘相关胃肠调节递质的影响, figureFileSmall=evKq+eDp9BDzRHEWBIQXkw==, figureFileBig=nRi8Ko5Ohk80zYxMTdKWnA==, tableContent=null), ArticleFig(id=1320882241589330049, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.4, caption=Effect of prebiotics and prune juice on intestinal barrier function in mice, figureFileSmall=jOvCJKRUEcsykBGSRQfRoA==, figureFileBig=XtvDKNfXy18WcDr9PdZa3w==, tableContent=null), ArticleFig(id=1320882241664827522, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图4, caption=复配益生元和西梅汁对小鼠肠道屏障系统的影响

注:a~f分别是MUC2、Claudin、Occludin、ZO-1、SCF、AQP3 mRNA相对表达量。

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注:a~c分别为乙酸、丙酸、丁酸含量。

, figureFileSmall=8AQzUsF5xTRyAifAX84uCw==, figureFileBig=6hO+/cfbke1rrFL7LyD9lg==, tableContent=null), ArticleFig(id=1320882242046509191, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.7, caption=Effect of prebiotics and prune juice on microbial diversity in mice, figureFileSmall=fspk++Nq7lpEUu55s7koww==, figureFileBig=juQcyLnf3TjOH7W3jVD4Kw==, tableContent=null), ArticleFig(id=1320882242122006664, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图7, caption=复配益生元和西梅汁对小鼠肠道菌群多样性的影响, figureFileSmall=fspk++Nq7lpEUu55s7koww==, figureFileBig=juQcyLnf3TjOH7W3jVD4Kw==, tableContent=null), ArticleFig(id=1320882242226864265, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.8, caption=LEfSe analysis of signature taxa in the groups, figureFileSmall=i4ZOPNhsF846KAPRa7zgmw==, figureFileBig=v8Upi6M9nr5tKxiAv/X3yg==, tableContent=null), ArticleFig(id=1320882242310750346, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图8, caption=肠道菌群LEfSe分析, figureFileSmall=i4ZOPNhsF846KAPRa7zgmw==, figureFileBig=v8Upi6M9nr5tKxiAv/X3yg==, tableContent=null), ArticleFig(id=1320882242403025035, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.9, caption=Effect of prebiotics and prune juice on the relative abundance of genera, figureFileSmall=z9+7isnUwnAU69woljEr3g==, figureFileBig=S6As2mR9stksVHvwFkfp4Q==, tableContent=null), ArticleFig(id=1320882242474328205, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图9, caption=复配益生元和西梅汁对不同菌属相对丰度的影响, figureFileSmall=z9+7isnUwnAU69woljEr3g==, figureFileBig=S6As2mR9stksVHvwFkfp4Q==, tableContent=null), ArticleFig(id=1320882242545631374, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Fig.10, caption=Correlation between the relative abundance of bacterial genera and constipation related indicators, figureFileSmall=jNouBKXYI6rtNKd98b8GtA==, figureFileBig=L6GjXYpBRq3JBMbIYlB0Ig==, tableContent=null), ArticleFig(id=1320882242600157328, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=图10, caption=菌属相对丰度与便秘相关指标的相关性

注:*表示菌属相对丰度与便秘相关指标存在显著相关,*:P<0.05,**:P<0.01,***:P<0.001。

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Gavage sample information

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物质量
(每100 mL)
益生元
配方1(g)
益生元配方
1+西梅汁(g)
益生元
配方2(g)
益生元配方2+西梅汁(g)
低聚木糖1.51.533
水苏糖2.52.533
低聚甘露糖0.750.750.050.05
低聚半乳糖4488
半乳甘露聚糖0.10.10.050.05
抗性糊精0.10.10.10.1
聚葡萄糖2.52.511
浓缩西梅汁03.503.5
), ArticleFig(id=1320882242780512402, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=表1, caption=

灌胃液信息

, figureFileSmall=null, figureFileBig=null, tableContent=
物质量
(每100 mL)
益生元
配方1(g)
益生元配方
1+西梅汁(g)
益生元
配方2(g)
益生元配方2+西梅汁(g)
低聚木糖1.51.533
水苏糖2.52.533
低聚甘露糖0.750.750.050.05
低聚半乳糖4488
半乳甘露聚糖0.10.10.050.05
抗性糊精0.10.10.10.1
聚葡萄糖2.52.511
浓缩西梅汁03.503.5
), ArticleFig(id=1320882242860204179, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=EN, label=Table 2, caption=

Primer sequences used in qPCR experiments

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引物名称引物序列
GapdhF: 5'-TGGCCTTCCGTGTTCCTAC-3'
R: 5'-GAGTTGCTGTTGAAGTCGCA-3'
ClaudinF: 5'-ATGGCGTCTATGGGACTACAG-3'
R: 5'-GAGCGCACAACTCAGGATG-3'
OccludinF: 5'-TTGAAAGTCCACCTCCTTACAGA-3'
R: 5'-CCGGATAAAAAGAGTACGCTGG-3'
MUC2F: 5'-GCCCACCTCACAAGCAGTAT-3'
R: 5'-GTCATAGCCAGGGGCAAACT-3'
ZO-1F: 5'-CTCAAGTTCCTGAAGCCCGT-3'
R: 5'-GCAAAAGACCAACCGTCAGG-3'
SCFF: 5'-AGCTTGACTACTCTTCTGGACA-3'
R: 5'-TGGCCTCTTCGGAGATTCTTTT-3'
AQP3F: 5'-GGGCCTTTGCCAACAATGAG-3'
R: 5'-CGGCTGTGCCTATGAACTGA-3'
BDNFF: 5'-GCCTTTGGAGCCTCCTCTAC-3'
R: 5'-CGCCGAACCCTCATAGACAT-3'
GDNFF: 5'-GTCTGGCAGCCAACAAACAG-3'
R: 5'-TAGCAGCCACAAAGGGAGTG-3'
), ArticleFig(id=1320882242931507348, tenantId=1146029695717560320, journalId=1260987677001138203, articleId=1320882230323429407, language=CN, label=表2, caption=

qPCR实验中涉及的基因引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=
引物名称引物序列
GapdhF: 5'-TGGCCTTCCGTGTTCCTAC-3'
R: 5'-GAGTTGCTGTTGAAGTCGCA-3'
ClaudinF: 5'-ATGGCGTCTATGGGACTACAG-3'
R: 5'-GAGCGCACAACTCAGGATG-3'
OccludinF: 5'-TTGAAAGTCCACCTCCTTACAGA-3'
R: 5'-CCGGATAAAAAGAGTACGCTGG-3'
MUC2F: 5'-GCCCACCTCACAAGCAGTAT-3'
R: 5'-GTCATAGCCAGGGGCAAACT-3'
ZO-1F: 5'-CTCAAGTTCCTGAAGCCCGT-3'
R: 5'-GCAAAAGACCAACCGTCAGG-3'
SCFF: 5'-AGCTTGACTACTCTTCTGGACA-3'
R: 5'-TGGCCTCTTCGGAGATTCTTTT-3'
AQP3F: 5'-GGGCCTTTGCCAACAATGAG-3'
R: 5'-CGGCTGTGCCTATGAACTGA-3'
BDNFF: 5'-GCCTTTGGAGCCTCCTCTAC-3'
R: 5'-CGCCGAACCCTCATAGACAT-3'
GDNFF: 5'-GTCTGGCAGCCAACAAACAG-3'
R: 5'-TAGCAGCCACAAAGGGAGTG-3'
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复配益生元缓解便秘效果和途径探究
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蔡华昊 1, 2 , 刘运柱 3 , 朱胜男 1 , 王榕 1, 2 , 李乾乾 1, 2 , 张莉 1, 2 , 王琳琳 1, 2, * , 崔树茂 1, 2
食品工业科技 | 营养与保健 2026,47(1): 420-432
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食品工业科技 |营养与保健 2026 , 47 (1) : 420 -432
复配益生元缓解便秘效果和途径探究
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蔡华昊1, 2 , 刘运柱3, 朱胜男1, 王榕1, 2, 李乾乾1, 2, 张莉1, 2, 王琳琳1, 2, * , 崔树茂1, 2
作者信息
  • 1江南大学食品学院,江苏无锡 214122
  • 2无锡特殊食品与营养健康研究院有限公司,江苏无锡 214112
  • 3山东英贝健健康食品有限公司,山东济南 251414
通讯作者:
王琳琳(1985−),女,博士,副研究员,研究方向:益生菌与健康,E-mail:。
作者简介:

蔡华昊(1998−),男,硕士,研究方向:益生菌与健康,E-mail:

Effect and Approach of Combined Prebiotics in Alleviating Constipation
Huahao CAI1, 2 , Yunzhu LIU3, Shengnan ZHU1, Rong WANG1, 2, Qianqian LI1, 2, Li ZHANG1, 2, Linlin WANG1, 2, * , Shumao CUI1, 2
Affiliations
  • 1School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
  • 2Wuxi Institute for Specialized Nutrition and Health, Wuxi 214112, China
  • 3Shandong Yingbeijian Health Food Co., Ltd., Jinan 251414, China
出版时间: 2026-01-01 doi: 10.13386/j.issn1002-0306.2024120375
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目的:便秘是一种常见的功能性胃肠疾病,需要可持续且无副作用的缓解手段。方法:本研究采用洛哌丁胺诱导小鼠便秘模型,评估了复配益生元对便秘的缓解作用。研究首先考察了复配益生元对便秘表观指标的影响,后续进一步对便秘相关胃肠调节递质、肠道屏障系统、结肠组织损伤情况、粪便内短链脂肪酸含量和肠道菌群进行了检测。结果:复配益生元可以通过下调有害菌Bilophila、Anaerovorax的相对丰度,上调有益菌Ileibacterium、Bifidobacterium的相对丰度,从而上调结肠内兴奋性胃肠调节递质含量(胃泌素和P物质),改善肠道屏障系统(上调粘蛋白2、闭锁蛋白、干细胞因子表达量,下调水通道蛋白3 mRNA相对表达量),改善结肠组织损伤,上调粪便中乙酸、丁酸含量,最终下调排首粒黑便时间(相比模型组缩短了27%),增加粪便含水量(相比模型组增加了46%),有效缓解便秘。而复配益生元与西梅汁复配后可以进一步上调有益菌Odoribacter、Faecalibaculum、Defluviitaleaceae_UCG-011的相对丰度,进一步上调结肠内胃泌素、胃动素含量,下调结肠内降钙素基因相关肽含量,上调粘蛋白2 mRNA相对表达量,上调粪便中乙酸、丁酸含量,增加小肠推进率(相比模型组增加了47%)和5 h内排便量(相比模型组增加了132%),从而更有效地缓解便秘。结论:复配益生元(每100 mL中主要含有低聚木糖3 g、水苏糖3 g、低聚半乳糖8 g)可缓解便秘,益生元与西梅汁复配后可以通过增强小肠推进率和提高菌群调节能力进而更有效地缓解便秘。本研究发现了西梅汁可以增强益生元缓解便秘的功效,为多种类低剂量益生元配方的开发提供了数据支持,为后续开发新型便秘缓解策略提供了科学依据。

便秘  /  益生元  /  西梅汁  /  胃肠调节递质  /  肠道机械屏障  /  肠道菌群

Objective: Constipation is a common functional gastrointestinal disorder, necessitating sustainable and side-effect-free relief methods. Methods: This study investigated the efficacy of combined prebiotics in a loperamide-induced constipation mouse model. Further assessments included gut microbiota composition, fecal short-chain fatty acid levels, intestinal barrier-related markers, colonic tissue damage, and gastrointestinal regulatory neurotransmitters. Results: Combined prebiotics alleviated constipation by downregulating the abundance of harmful bacteria (Bilophila, Anaerovorax) and upregulating the abundance of beneficial bacteria (Ileibacterium, Bifidobacterium), thereby increasing excitatory gastrointestinal neurotransmitters (upregulating gastrin and substance P), improving the intestinal barrier (upregulating MUC2, Occludin, and SCF mRNA expression while downregulating AQP3 mRNA relative expression), repairing colonic tissue damage, and elevating fecal acetate and butyrate levels. These changes led to a 27% reduction in time to first black stool excretion and 46% increase in fecal water content compared to the model group. When combined with prune juice, the prebiotics formulation further enhanced the abundance of beneficial bacteria (Odoribacter, Faecalibaculum, Defluviitaleaceae_UCG-011), increased gastrin and motilin levels, decreased calcitonin gene-related peptide, upregulated MUC2 mRNA, elevated fecal acetate and butyrate, improved small intestinal propulsion rate (by 47% compared to the model group), and increased fecal output within 5 hours (by 132% compared to the model group), demonstrating superior constipation relief. Conclusion: The study demonstrates that the combined prebiotics (containing 3 g xylooligosaccharides, 3 g stachyose, and 8 g galactooligosaccharides per 100 mL) effectively relieve constipation. Prebiotics combined with prune juice further enhancing efficacy through improved intestinal motility and microbiota modulation. These findings support the development of multi-component prebiotic formulations and reveal prune juice's potential to amplify prebiotic effects, providing a scientific basis for novel constipation management strategies.

constipation  /  prebiotics  /  prune juice  /  gastrointestinal regulatory neurotransmitters  /  intestinal barrier  /  gut microbiota
蔡华昊, 刘运柱, 朱胜男, 王榕, 李乾乾, 张莉, 王琳琳, 崔树茂. 复配益生元缓解便秘效果和途径探究. 食品工业科技, 2026 , 47 (1) : 420 -432 . DOI: 10.13386/j.issn1002-0306.2024120375
Huahao CAI, Yunzhu LIU, Shengnan ZHU, Rong WANG, Qianqian LI, Li ZHANG, Linlin WANG, Shumao CUI. Effect and Approach of Combined Prebiotics in Alleviating Constipation[J]. Science and Technology of Food Industry, 2026 , 47 (1) : 420 -432 . DOI: 10.13386/j.issn1002-0306.2024120375
便秘是一种常见的消化系统问题,全世界大约20%的人口受到便秘的困扰[1]。只有约三分之一的便秘患者会选择就医,许多患者通过自行增加纤维摄入量或使用非处方泻药来自我治疗症状,但常规药物往往表现出停药就失效或者存在副作用等问题[2]。近年来益生元因其安全、无副作用、服用方便而受到关注。
益生元是一类不能完全被人体消化吸收,可以被肠道菌群消化利用产生益生效果的物质,对人体副作用较小[3]。目前有多种益生元可以缓解便秘,研究发现每日分别摄入5 g半乳甘露聚糖[4]、12 g聚葡萄糖[3]、5 g低聚木糖[5]、18 g低聚半乳糖[6]、15 g抗性糊精[6]均可缓解便秘。然而当前的研究多集中于单一种类,高剂量益生元缓解便秘,而忽视了所涉及的剂量是否符合既有法规的限制,比如《中华人民共和国食品安全法》设置了每日最高摄入量,低聚半乳糖摄入量应≤15 g/d,低聚甘露糖摄入量应≤1.5 g/d。相比之下,多种类、低剂量益生元复配配方因更符合法规要求而备受关注,然而目前研究对复配益生元起效剂量和配比优化的探索仍然不足。课题组前期研究以不同低聚糖替代培养基中的葡萄糖作为唯一碳源,检测缓解便秘较好的长双歧杆菌在此改良培养基中的代时,结果表明:在低聚木糖、水苏糖、低聚甘露糖和低聚半乳糖作为唯一碳源时长双歧杆菌的生长代时较短,推测这些益生元可促进长双歧杆菌在肠道的定植,而这是益生元治疗便秘的重要途径之一[7]。
纯益生元饮品存在风味单一、有“淀粉味”的问题,降低了市场接受度[8]。本研究引入浓缩西梅汁作为天然风味改良剂,其富含的糖,糖醇、多酚、有机酸等成分不仅能提供酸甜适口的感官特性,还可通过增强小肠蠕动[9]提高粪便含水量[10]的途径增强益生元饮品缓解便秘效果。
基于上述考量,本研究设计了两个多种类、低剂量复配益生元配方:益生元配方1在每100 mL中主要含有低聚木糖1.5 g、水苏糖2.5 g、低聚甘露糖0.75 g、低聚半乳糖4 g,益生元配方2在每100 mL中主要含有低聚木糖3 g、水苏糖3 g、低聚半乳糖8 g。同时将两种配方与西梅汁复配,在便秘小鼠模型中评估复配益生元和西梅汁对肠道动力、粪便含水率、胃肠调节递质、肠道屏障系统、粪便中短链脂肪酸和肠道菌群的影响。本研究意在探究可以缓解便秘的多种类,低剂量益生元配方的具体配比,同时探究西梅汁对益生元可能的增效作用。
实验动物6周龄雄性C57BL/6小鼠36只 浙江维通利华技术有限公司(生产许可证号:SCXK(浙)2024-0001),饲养于SPF环境,维持温度23~27 ℃,相对湿度45%~55%,每天12 h昼夜循环光照,自由饮水并喂食常规动物饲料;小鼠常规动物饲料LAD 0021 购自南通特洛菲饲料科技有限公司;低聚木糖、水苏糖、低聚甘露糖、低聚半乳糖 食品级,纯度>95%,上海源叶生物科技有限公司;半乳甘露聚糖、抗性糊精、聚葡萄糖 食品级,纯度>95%,山东百龙创园生物科技股份有限公司;浓缩西梅汁(物质组成:水27.0%,碳水化合物70.2%,蛋白质1.9%,膳食纤维6.4%,糖醇13.4%) 广东英贝健生物科技有限公司;盐酸洛哌丁胺胶囊 西安杨森制药有限公司;阿拉伯树胶粉、活性炭粉 化学纯,国药集团化学试剂公司;乙酸、丙酸、丁酸 色谱纯,国药集团化学试剂公司;小鼠胃动素(Motilin,MTL)、小鼠胃泌素(Gastrin,Gas)、小鼠P物质(Substance P,SP)、小鼠降钙素基因相关肽(Calcitonin Gene Related Peptide,CGRP)ELISA试剂盒 南京森贝伽生物;粪便提取试剂盒 美国MP Biomedicals公司;DNA胶回收试剂盒 中国天根生化科技有限公司;组织RNA提取试剂盒、逆转录、qPCR试剂盒 南京诺唯赞生物科技有限公司。
FZTradi-6L真空冷冻干燥机 美国 LABCONCO 公司;Multiscan Go多功能酶标仪、Sorvall MX120+超高速离心机 美国 Thermo Fisher公司;CFX Opus实时荧光定量基因扩增仪 Bio-Rad 公司;SCIENTZ-48高通量组织研磨仪 宁波新芝生物科技股份有限公司;IIumina MiSeq PE300高通量测序仪 美国Illumina公司;P2010 Ultra气质联用仪(使用Rtx-WAX毛细管柱) 日本岛津公司。
动物实验参考Wang等[11]的实验和《保健食品功能检验与评价方法》的“有助于润肠通便”章节进行设计,并进行部分修改。动物实验遵循《实验动物护理和使用指南》进行,并得到了江苏寄生疾病研究所动物伦理委员会批准,伦理编号为:IACUC-JIPD-2023-098。
动物实验流程如图1所示。适应性饲养一周,期间每天重新打乱小鼠分组,确保小鼠肠道微生物处于同一水平,适应期无明显异常后小鼠随机分笼后开始实验。小鼠共被分为6组,溶剂对照组,模型组,灌胃益生元配方1的干预组(简称为配方1组),灌胃添加了西梅汁的益生元配方1的干预组(简称为配方1+西梅汁组),灌胃益生元配方2的干预组(简称为配方2组),灌胃添加了西梅汁的益生元配方2的干预组(简称为配方2+西梅汁组),每组灌胃液信息如表1所示。
第1~3周,预防干预:每日,溶剂对照组和模型组灌胃0.25 mL无菌生理盐水;干预组灌胃0.25 mL灌胃液。
第4周,药物干预:每日,溶剂对照组灌胃0.25 mL无菌生理盐水,模型组和干预组灌胃0.25 mL的10 mg/kg BW剂量的洛哌丁胺进行造模,半小时后溶剂对照组和模型组灌胃0.25 mL生理盐水,干预组灌胃0.25 mL灌胃液。
第4周最后一天,在禁食不禁水12 h后,溶剂对照组灌胃0.25 mL无菌生理盐水,其他组灌胃0.25 mL的10 mg/kg BW剂量的洛哌丁胺进行造模。半小时后溶剂对照组和模型组灌胃0.25 mL无菌生理盐水和活性炭墨水,干预组灌胃0.25 mL灌胃液和活性炭墨水。半小时后处死小鼠并收集所需材料。
粪便含水量实验测定参考Wang等[11]的实验,灌胃后,将动物放置于垫有滤纸的洁净笼盒中,使用已称重量的无菌离心管收集新鲜粪便,称量得到粪便湿重。使用真空冷冻干燥机进行冻干,称重,得到粪便干重。根据公式(1)计算粪便含水量:
$ \begin{split}&\mathrm{粪}\mathrm{便}\mathrm{含}\mathrm{水}\mathrm{量}(\text{%})=\\&\frac{\mathrm{粪}\mathrm{便}\mathrm{冻}\mathrm{干}\mathrm{前}\mathrm{重}\mathrm{量}(\mathrm{g})-\mathrm{粪}\mathrm{便}\mathrm{冻}\mathrm{干}\mathrm{后}\mathrm{重}\mathrm{量}(\mathrm{g})}{\mathrm{粪}\mathrm{便}\mathrm{冻}\mathrm{干}\mathrm{前}\mathrm{重}\mathrm{量}(\mathrm{g})}\times 100 \end{split}$
排首粒黑便时间实验测定参考Wang等[11]的实验,在实验结束的前一天,溶剂对照组灌胃0.25 mL生理盐水,模型组和干预组灌胃0.25 mL洛哌丁胺进行造模。半小时后溶剂对照组和模型组灌胃0.25 mL生理盐水和活性炭墨水,干预组灌胃0.25 mL灌胃液和活性炭墨水。将每只实验动物单独放入垫有滤纸的洁净笼盒中,记录开始时间。待小鼠排出第一颗黑便后,记录相应时间为结束时间,两个时间的间隔即为排首粒黑便时间。
小肠推进率测定参考Wang等[11]的实验,实验取出小鼠从胃到肛门的消化道,将小肠轻拉成直线,幽门到盲肠的长度记录为小肠总长度,幽门到墨汁前沿的长度记录为活性炭溶液前端推进距离,根据公式(2)计算小肠推进率:
$ \begin{split}&\mathrm{小}\mathrm{肠}\mathrm{推}\mathrm{进}\mathrm{率}(\text{%})=\\&\frac{\mathrm{活}\mathrm{性}\mathrm{炭}\mathrm{溶}\mathrm{液}\mathrm{前}\mathrm{端}\mathrm{推}\mathrm{进}\mathrm{距}\mathrm{离}(\mathrm{c}\mathrm{m})}{\mathrm{小}\mathrm{肠}\mathrm{总}\mathrm{长}\mathrm{度}(\mathrm{c}\mathrm{m})}\times 100\end{split}$
胃肠调节递质测定参考Wang等[11]的实验,取约20 mg结肠组织,用200 μL预冷PBS缓冲液混合,使用组织破碎仪匀浆,在4 ℃,12000×g下离心15 min,取组织上清。用ELISA试剂盒检测组织上清中的MTL、GAS、SP和CGRP的含量。使用碧云天的BCA试剂盒测定结肠组织蛋白质浓度。
结肠组织mRNA表达量分析参考张童等[12]的研究,用RNA提取试剂盒提取结肠组织中的mRNA,使用逆转录试剂盒将mRNA逆转录为cDNA。使用qPCR试剂盒进行RT-qPCR实验。实验中涉及的基因引物序列如表2所示。
组织病理学分析参考张童等[12]的方法,取出5 mm左右中段结肠,使用4%多聚甲醛固定过夜。将样品使用梯度酒精脱水,二甲苯洗涤,石蜡包埋,切片,HE染色。使用数字组织切片扫描仪观察切片。
短链脂肪酸含量测定方法张童等[12]的研究,通过气相质谱联用法测定小鼠粪便中短链脂肪酸的含量。取冻干后的小鼠粪便30 mg,加入0.5 mL饱和氯化钠和20 μL 10%硫酸,充分混合破碎。在冰上添加1 mL乙醚并再次充分混合。在4 ℃下14000×g离心15 min,取乙醚上清转移至离心管中,加入0.25 g无水硫酸钠脱去多余水分。再次在4 ℃下14000×g离心5 min,取乙醚上清液到气相小瓶中。使用外标法制作乙酸、丙酸、丁酸的标准曲线。采用 Rtx-WAX 毛细管柱结合气相色谱-质谱联用仪QP2010 Ultra进行分析,气相色谱质谱条件参考张童等[12]的研究:载气为氦气,流速为0.89 mL/min,初始温度为100 ℃,以7.5 ℃/min升温至140 ℃,随后以60 ℃/min升温至200 ℃,保持3 min。进样口温度设置为240 ℃,质谱仪离子源温度为220 ℃,接口温度为250 ℃,质谱扫描范围为2~100 m/z。
粪便菌群测定方法参考卢慧敏等[13]的实验,在实验第29 d,取2~4颗新鲜粪便,使用粪便提取试剂盒提取其中的总DNA。使用通用引物(341F正向引物序列:5'-CCTAYGGGRBGCASCAG-3'和806R反向引物序列:5'-GGACTACNNGGGGTATCTAAT-3')对16S rRNA的V3-V4区基因进行扩增。使用琼脂糖凝胶电泳和胶回收试剂盒纯化扩增产物。将DNA等浓度汇集后再进行配对末端测序。使用 Quantitative Insights into Microbial Ecology version 2(QIIME2)程序进行16S rRNA测序分析。
图表中的数据使用平均值±标准差(Mean±SD)表示,通过t检验比较模型组和溶剂对照组差异,#表示模型组与溶剂对照组有显著差异:#:P<0.05,##:P<0.01,###:P<0.001。通过单因素方差分析结合Duncan事后检验比较模型组和各干预组差异,*表示模型组与干预组有显著差异,*:P<0.05,**:P<0.01,***:P<0.001。
洛哌丁胺可以与肠道内阿片类受体结合,抑制胃肠神经信号传导,进而抑制肠道平滑肌收缩,增加肠道转运时间,促进粪便硬化,产生慢传输性便秘症状[14]。本研究参考了《保健食品功能检验与评价方法(2023年版)》中“有助于润肠通便”动物实验的建模方法,使用洛哌丁胺构建慢传输性便秘模型。
结果如图2所示,相比于溶剂对照组,模型组小肠推进率极显著下降(图2a,P<0.001),排首粒黑便时间极显著上升(图2b,P<0.001),粪便含水量高度显著下降(图2c,P<0.01),5 h内粪便重量和数量极显著下降(图2d、e,P<0.001),表明应用洛哌丁胺成功构建了便秘模型。使用复配益生元与西梅汁干预后,与模型组相比,所有干预组都显著下调了排首粒黑便时间(图2b,P<0.05),都对小肠推进率、粪便含水量、5 h内粪便重量和数量表现出上调的趋势。其中配方1+西梅汁、配方2+西梅汁显著提高了小肠推进率(图2a,P<0.05),配方1+西梅汁、配方2、配方2+西梅汁显著上调了粪便含水量(图2c,P<0.05),配方2+西梅汁显著上调了5 h粪便重量和数量(图2d、e,P<0.05)。
《保健食品功能检验与评价方法(2023年版)》中“有助于润肠通便”阳性结果的评价标准为:5 h排粪便量和粪便含水量一项结果阳性,同时小肠推进率和排首粒黑便时间一项结果为阳性,可判定该受试样品有助于润肠通便动物实验结果阳性。在本研究中配方1+西梅汁、配方2、配方2+西梅汁显著改善了粪便含水量和排首粒黑便时间,说明配方1+西梅汁、配方2、配方2+西梅汁可缓解便秘。其中配方1、配方2都不能显著改善小肠推进率,而添加西梅汁后均能显著改善小肠推进率,说明西梅汁可能通过上调小肠推进率的方式增强益生元缓解便秘效果,这个结果与Na等[10]的研究结果一致。
胃肠调节递质是一类由胃肠道粘膜细胞、胰腺分泌细胞、胃肠壁神经细胞等细胞分泌的高效能生物活性物质,在消化系统中发挥着感知肠内容物、调节胃肠运动、系统代谢、食物摄入、营养物质的消化和吸收等重要作用[15]。本研究选择的MTL、GAS、SP是兴奋性胃肠调节递质,CGRP是抑制性胃肠调节递质。MTL可以促进胆囊排空,增加胰岛素释放,增加胃肠道蠕动;GAS可以促进氨基酸吸收,扩张胃部容量;SP可以促进平滑肌松弛,也可以增加肠平滑肌对乙酰胆碱敏感性进而促进平滑肌收缩,从而增强肠道蠕动;CGRP与疼痛感知呈正相关,CGRP含量的升高会导致胃部不适,恶心,便秘等症状[15−17]。
如图3所示,模型组小鼠结肠组织中兴奋性胃肠调节递质MTL、GAS、SP含量显著降低(图3a~c,P<0.05),抑制性胃肠调节递质CGRP含量高度显著上升(图3d,P<0.01),表明应用洛哌丁胺在诱导便秘动物模型时,小鼠除了具有便秘的表观症状外,还存在结肠内胃肠调节递质含量的失调。使用复配益生元与西梅汁干预后,相对于模型组,干预组小鼠结肠组织中兴奋性胃肠调节递质MTL、GAS、SP的含量都有所上调,结肠组织中抑制性胃肠调节递质CGRP的含量都显著下调(图3d,P<0.05)。其中配方2显著上调了兴奋性胃肠调节递质MTL和SP的含量(图3a、b,P<0.05),配方1+西梅汁、配方2+西梅汁显著上调了兴奋性胃肠调节递质MTL、GAS、SP的含量(图3a~c,P<0.05)。
便秘患者结肠组织中胶质细胞源性神经营养因子(Glial cell line-Derived Neurotrophic Factor,GDNF)和脑源性神经营养因子(Brain Derived Neurotrophic Factor,BDNF)含量减少[18],GDNF可以促进神经元细胞存活,对结肠肌层神经分布和神经节细胞功能具有重要影响,BDNF可以通过增加肠道肌电活动,加速结肠排空,从而增加排便频率缓解慢传输性便秘,GDNF和BDNF是大分子蛋白并且容易发生降解,这里使用qPCR法测定两者在结肠中的mRNA表达量[18−19]。
如图3所示,模型组小鼠结肠组织中神经营养因子GDNF、BDNF的mRNA相对表达量高度显著降低(图3e、f,P<0.01)。这与张童等[12]的发现一致。使用复配益生元与西梅汁干预后,配方2显著上调了结肠组织中GDNF和BDNF的mRNA相对表达量(图3e、f,P<0.05),配方2+西梅汁显著上调了结肠组织中GDNF的mRNA相对表达量(图3e,P<0.05),而对BDNF的mRNA相对表达量只有上调的趋势,没有显著性差异。
上述结果说明了益生元配方可以通过调节胃肠调节递质改善便秘,其中配方2对所有胃肠调节递质的调节能力都强于配方1。张华南等[20]也发现,低聚木糖、水苏糖等益生元可以通过上调兴奋性胃肠调节递质,下调抑制性胃肠调节递质,缩短排首粒黑便时间,缓解便秘。
配方1不能显著调节兴奋性胃肠调节递质(MTL、GAS、SP)而配方1+西梅汁可以显著调节兴奋性胃肠调节递质;相比于配方2,配方2+西梅汁小鼠结肠内兴奋性胃肠调节递质含量有所上调。说明西梅汁可能通过进一步提升益生元对兴奋性胃肠调节递质的调节能力,促进胃肠蠕动,从而上调小肠推进率,增强益生元配方缓解便秘效果。Piirainen等[21]发现西梅汁不仅能够缓解便秘,其富含的膳食纤维成分还可通过喂养肠道菌群,间接影响胃肠调节递质的水平[22]。为了解释西梅汁增强益生元配方调节胃肠调节递质能力的可能途径,本研究后续测定了小鼠肠道菌群和肠道菌群代谢物。
肠道机械屏障主要由肠上皮细胞,上皮细胞之间的紧密连接蛋白和肠道粘液层组成。肠上皮细胞是肠道屏障最重要的组成部分,主要功能为物理隔离肠内环境和内循环,吸收肠内营养物质,释放粘蛋白、抗菌肽等分泌物。Cajal间质细胞是调节肠道上皮细胞稳态的关键细胞,而SCF(Stem Cell Factor,干细胞因子)则能维持Cajal间质细胞正常发育成熟[23]。肠上皮细胞通过以AQP3(Aquaporin-3,水通道蛋白3)为主的水通道蛋白吸收肠道内水分,洛哌丁胺可以通过上调AQP3的表达量,进而加快肠道对水分的吸收,减少粪便含水率,进一步加重便秘[24]。肠道粘液层主要由肠上皮细胞中的成熟杯状细胞分泌的MUC2(Mucin2,粘蛋白2)组成,肠道粘液层可以避免肠内物质直接与肠上皮细胞接触,同时,MUC2还可以润滑肠道,提高粪便含水率,进而改善便秘[25]。肠上皮细胞之间由以Claudin(封闭蛋白)、Occludin(闭锁蛋白)为主的紧密连接蛋白相互连接,ZO-1(Zonula Occludens-1,闭锁小带蛋白1)则将细胞间的紧密连接蛋白固定到细胞内的蛋白骨架中,紧密连接蛋白的正常表达可以防止肠内物质渗漏到内循环[26]。
如图4所示,模型组MUC2、Claudin、Occludin、SCF mRNA相对表达量显著下降(图4a~c、e,P<0.05),AQP3 mRNA相对表达量高度显著上升(图4f,P<0.01),表明便秘造成了肠道屏障损伤。而灌胃复配益生元和西梅汁后,相对于模型组,所有干预组都上调了MUC2、Occludin、SCF的mRNA相对表达量,并显著下调了AQP3的mRNA相对表达量(P<0.05)。其中配方1+西梅汁显著上调了MUC2、SCF的mRNA相对表达量(图4a、e,P<0.05),配方2显著上调了MUC2、Occludin、SCF的mRNA相对表达量(图4a、e、f,P<0.05),配方2+西梅汁显著上调了MUC2、Occludin、SCF的mRNA相对表达量(图4a、e、f,P<0.05)。
结果显示,在改善肠道机械屏障方面,配方2、配方1+西梅汁、配方2+西梅汁都能调节便秘所引起的肠道机械屏障损伤,其中益生元配方2效果优于配方1。并且西梅汁可以提升益生元配方对MUC2的调节能力。
干预组的益生元配方通过维护肠道粘液层和紧密连接改善肠道机械屏障,这一发现与Cao等[27]的研究相似,益生元可能通过调节肠道菌群维持肠道稳态发挥改善肠道机械屏障的作用,进而通过调节5-羟色胺途径、维护肠道神经系统、减少肠道轻度炎症等多种途径促进肠道正常蠕动,减轻便秘症状。
GDNF、BDNF是Cajal间质细胞的重要营养物质而SCF是Cajal间质细胞的标志物[18−19,23]。类似的,Su等[28]的研究也发现,益生元可以通过维持肠道屏障功能减少Cajal间质细胞受损,并进一步改善肠道运动功能。
AQP3是一类膜结合水通道分子,洛哌丁胺通过上调AQP3 mRNA的表达量,进而加快肠道对水分的吸收,破坏肠腔液体稳态,减少粪便含水率,加重便秘症状[24]。本文的结果与Lee等[29]相似,益生元可以通过恢复AQP3的表达水平,维持肠腔液体稳态,维护肠道水通道屏障的完整性,提高粪便含水率,缓解便秘症状。
洛哌丁胺诱导的便秘会伴随着肠道肌肉层变薄,肠腺损伤和杯状细胞减少,这些变化会进一步损伤肠道粘液层,减缓肠道蠕动力,进而加重便秘症状[30]。
由图5所示,相对于溶剂对照组,模型组中出现了结肠肌肉层变薄(蓝色箭头)成熟杯状细胞减少(黄色箭头),肠腺排列不整齐(绿色箭头)说明便秘减少了肠道内粘液分泌,并对结肠组织造成了损伤。使用复配益生元与西梅汁干预后,相比于模型组,配方1、配方1+西梅汁组结肠组织损伤情况仍然较重,依然可见结肠肌肉层变薄(蓝色箭头)成熟杯状细胞减少(黄色箭头)和肠腺排列不整齐(绿色箭头)。配方2和配方2+西梅汁组结肠组织损伤情况较轻,偶见成熟杯状细胞减少(黄色箭头)。结果显示,益生元配方2和配方2+西梅汁可以较好地缓解便秘对小鼠结肠组织造成的损伤。
短链脂肪酸是缓解便秘的重要靶点,可以促进结肠上皮细胞增长并提供代谢能量,是结肠粘膜的重要营养物质,乙酸和丁酸在缓解便秘的过程中起着关键作用[31]。如图6所示,对比溶剂对照组,模型组中乙酸、丁酸含量显著下降(图6a、c,P<0.05),丙酸含量有所下降但是没有显著性差异。而灌胃复配益生元和西梅汁后,相对于模型组,所有干预组粪便内乙酸、丁酸含量都有所上调,其中配方2、配方2+西梅汁显著上调了粪便内乙酸和丁酸含量(图6a、c,P<0.05)。
结果显示,在改善粪便内短链脂肪酸方面,益生元配方2和配方2+西梅汁能显著上调粪便内乙酸和丁酸含量。Liu等[32]的研究发现结肠中的短链脂肪酸主要由双歧杆菌、乳酸菌等肠道有益菌发酵产生,可以通过短链脂肪酸-G蛋白偶联受体信号通路调节肠道神经系统功能,促进兴奋性胃肠调节递质并增强肠道屏障功能。在本研究中,配方2和配方2+西梅汁含有的益生元[20]和西梅汁[21]均能喂养肠道菌群,促进有益菌的增殖和代谢,可能通过粪便内短链脂肪酸这一途径调节胃肠调节递质,增强肠道屏障系统。为深入探究益生元和西梅汁对肠道菌群的调节作用和对便秘的缓解作用,本研究后续进一步分析了便秘小鼠肠道菌群的变化,旨在完善益生元和西梅汁通过肠道菌群调节便秘相关指标(胃肠调节递质,肠道屏障系统,菌群代谢物等)最终改善便秘表观指标的具体途径。
如图7a~d所示,结果显示,各组小鼠肠道菌群的α-多样性没有显著差异。如图7e所示,β-多样性结果显示各组间无明显分离趋势。这可能是由于在本研究中溶剂对照组和模型组的肠道菌群多样性没有显著差异,需要进一步从关键差异菌属的角度进行分析便秘和复配配方对肠道菌群的影响。类似的,Meji等[33]也发现与健康人相比,便秘患者肠道菌群的多样性没有显著差异,需要通过岭回归等方法确定便秘患者肠道菌群的特征菌属。
LEfSe分析结果如图8所示,通过LEfSe分析发现了数个标志性菌属,模型组的标志性菌属有:Bilophila,Oscillibacter和Romboutsia。配方1组的标志性菌属有Allobaculum。配方1+西梅汁组的标志性菌属有Turicibacter。配方2组的标志性菌属有Dubosiella。配方2+西梅汁组的标志性菌属有Ileibacterium,Bifidobacterium和Odoribacter等。为深入探究益生元配方和西梅汁对肠道菌群的具体调控作用,研究进一步分析了这些标志性菌属的相对丰度变化。
本研究进一步分析了数种标志性菌属的相对丰度变化,结果如图9所示,在模型组中Bilophila,Anaerovorax相对丰度高度显著上升(图9a、b,P<0.01),Ileibacterium、Odoribacter、Faecalibaculum、Defluviitaleaceae_UCG-011相对丰度显著下降(图9c、e~g,P<0.05)。
其中,在配方1干预后Anaerovorax相对丰度极显著下降(图9b,P<0.001),Bilophila相对丰度下降, Faecalibaculum、Bifidobacterium相对丰度上升(图9a、d、f)。在配方1+西梅汁干预后Bilophila、Anaerovorax相对丰度显著下降(图9a、b,P<0.05)。在配方2干预后Bilophila、Anaerovorax相对丰度显著下降(图9a、b,P<0.05)。Ileibacterium、Bifidobacterium相对丰度显著上升(图9c、d,P<0.05)。在配方2+西梅汁干预后Bilophila、Anaerovorax相对丰度显著下降(图9a、b,P<0.05)。Ileibacterium、Bifidobacterium、Odoribacter、Faecalibaculum、Defluviitaleaceae_UCG-011相对丰度显著上升(图9c~g,P<0.05)。
结果表明,四种干预方式均能调节标志性菌属的相对丰度,但各自的影响侧重点存在差异。
为了进一步探究不同干预方式如何通过调节标志性菌属的相对丰度来缓解便秘症状,本研究进一步使用Spearman相关性分析法分析了菌属的相对丰度与便秘相关指标间的关联性。结果如图10所示。
Anaerovorax是一种有害菌,其相对丰度与骨质疏松,儿童肥胖等疾病呈正相关[34]。在本研究中,Anaerovorax相对丰度与小肠推进率、粪便含水量、5 h粪便量,结肠内MTL、GAS含量,MUC2、SCF mRNA相对表达量,粪便内乙酸含量呈显著负相关,与排首粒黑便时间、结肠内CGRP含量呈显著正相关(图10,P<0.05)。
配方1可能通过下调Anaerovorax相对丰度调节胃肠调节递质的含量,改善肠道机械屏障,增加粪便中乙酸含量,减少排首粒黑便时间。
Bilophila是一种机会致病菌,可以将有机硫转化为硫化氢进而影响肠道健康,在便秘的形成过程中发挥重要作用[35]。在本研究中,Bilophila相对丰度与小肠推进率、粪便含水量,结肠内GDNF、SCF mRNA相对表达量,粪便内乙酸含量呈显著负相关,与排首粒黑便时间、结肠内CGRP含量呈显著正相关(图10,P<0.05)。
配方1+西梅汁可能通过下调Bilophila、Anaerovorax的相对丰度调节胃肠调节递质的含量,改善肠道机械屏障,增加粪便中乙酸含量,进而改善便秘表观指标,缓解便秘。
Huang等[36]发现Ileibacterium可以通过产生丁酸,4-甲基戊酸和己酸,维护肠道健康,减少肠道内炎症,发挥益生作用。在本研究中,Ileibacterium的相对丰度与粪便含水量,结肠内GDNF、BDNF的mRNA相对表达量,Occludin的mRNA相对表达量,粪便内乙酸和丁酸含量呈显著正相关,与排首粒黑便时间,结肠内CGRP含量呈显著负相关(图10,P<0.05)。
Bifidobacterium是一种公认的益生菌,补充Bifidobacterium可以改善肠道环境并且增加排便频率和粪便含水率[37]。在本研究中,Bifidobacterium的相对丰度与小肠推进率、粪便含水量,结肠内MTL含量、GDNF的mRNA相对表达量,MUC2、Occludin、SCF的mRNA相对表达量,粪便内乙酸和丁酸含量呈显著正相关,与排首粒黑便时间,结肠内CGRP含量呈显著负相关(图10,P<0.05)。
配方2可能通过下调Bilophila、Anaerovorax的相对丰度,上调Ileibacterium、Bifidobacterium相对丰度调节胃肠调节递质的含量,改善肠道机械屏障,增加粪便中乙酸和丁酸含量,进而改善便秘表观指标,缓解便秘。
Wang等[31]发现Odoribacter相对丰度与肠道中短链脂肪酸含量呈正相关,并且与小肠推进率和粪便含水率正相关,可以缓解便秘。类似的,在本研究中Odoribacter的相对丰度与5 h粪便量,结肠内MTL含量、GDNF、BDNF、MUC2的mRNA相对表达量和粪便内丁酸含量呈显著正相关(图10,P<0.05)。
Ma等[38]发现,在乳果糖干预后Faecalibaculum相对丰度上升,并且Faecalibaculum可以维护肠屏障完整并促进结肠蠕动。Faecalibaculum的相对丰度与小肠推进率,结肠内MUC2、Occludin、SCF的mRNA相对表达量,粪便内乙酸含量呈显著正相关,与结肠内CGRP含量呈显著负相关(图10,P<0.05)。
Defluviitaleaceae_UCG-011可以通过调节胃肠蠕动和肠道水分吸收,进而改善胃肠健康[39]。Defluviitaleaceae_UCG-011的相对丰度与小肠推进率,结肠内MUC2的mRNA相对表达量,粪便内乙酸含量呈显著正相关(图10,P<0.05)。
配方2+西梅汁可能通过下调Bilophila、Anaerovorax的相对丰度,上调Ileibacterium、Bifidobacterium、Odoribacter、Faecalibaculum、Defluviitaleaceae_UCG-011相对丰度调节胃肠调节递质的含量,改善肠道机械屏障,调节肠道水吸收,增加粪便中乙酸和丁酸含量,进而改善便秘表观指标,缓解便秘。
综上所述,四种干预方式均能通过上调有益菌相对丰度,下调有害菌相对丰度的方式调节便秘相关指标进而缓解便秘。其中配方1对菌群的调节作用相对较弱,不能缓解便秘。然而,当在配方1中添加西梅汁后,配方1对菌群的调节效果得到增强,使得配方1+西梅汁能够有效缓解便秘。同样地,在配方2中额外添加西梅汁后,进一步提升了配方2的菌群调节能力,从而使配方2+西梅汁对便秘的缓解效果优于单独使用配方2。
西梅汁所含的糖醇、多酚、有机酸等小分子,能够调节小肠渗透压,加速食糜通过小肠,缓解便秘[9]。相较之下,益生元作用主要集中在结肠,通过喂养肠道菌群发挥作用,而在本研究中,益生元配方1和2对小肠推进率的直接改善效果不显著。这表明西梅汁和益生元的起效位置存在互补性,此外,西梅汁可以减少益生元在小肠中的停留时间,进一步避免益生元在小肠中可能的消化。这些是西梅汁增强益生元配方缓解便秘能力的途径。
本研究通过合理设计配比后得到了一个多种类低剂量益生元配方,并且发现了西梅汁对益生元配方的增效作用。通过标志性菌属相对丰度与便秘相关指标的相关性分析发现,益生元配方2(每100 mL中主要含有低聚木糖3 g、水苏糖3 g、低聚半乳糖8 g)可以通过下调肠道内有害菌Bilophila、Anaerovorax的相对丰度、上调有益菌Ileibacterium、Bifidobacterium的相对丰度,进而上调结肠内兴奋性胃肠调节递质(MTL、SP)含量,GDNF、BDNF的mRNA相对表达量,改善肠道屏障系统(上调MUC2、Claudin、SCF、AQP3的mRNA相对表达量),改善结肠组织损伤,上调粪便中乙酸、丁酸含量,从而缓解便秘。而益生元配方2与西梅汁复配后可以通过进一步上调有益菌Odoribacter、Faecalibaculum、Defluviitaleaceae_UCG-011的相对丰度,从而上调结肠内MTL、GAS含量,下调结肠内CGRP含量,上调MUC2的mRNA相对表达量,上调乙酸、丁酸含量,增加小肠推进率,从而更有效地缓解便秘。
本研究发现相比于单独使用复配益生元,在益生元中额外复配西梅汁可以更有效地缓解便秘。西梅汁对益生元的增效作用主要表现在增强小肠推进率和提高菌群调节能力。后续将进一步探索益生元之间潜在的协同增效机制及其最优配比规律;通过代谢组学等方式完善差异菌属如何影响便秘症状的机制;深入研究益生元和西梅汁之间的可能存在的协同增效机制。本研究为缓解便秘的复合益生元配方设计提供了理论基础,为益生元和西梅汁在缓解便秘中作用方式和相互作用关系提供了新的见解,为后续开发新型便秘缓解策略提供了科学依据。

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2026年第47卷第1期
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doi: 10.13386/j.issn1002-0306.2024120375
  • 接收时间:2024-12-30
  • 首发时间:2026-10-24
  • 出版时间:2026-01-01
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  • 收稿日期:2024-12-30
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    1江南大学食品学院,江苏无锡 214122
    2无锡特殊食品与营养健康研究院有限公司,江苏无锡 214112
    3山东英贝健健康食品有限公司,山东济南 251414

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王琳琳(1985−),女,博士,副研究员,研究方向:益生菌与健康,E-mail:。
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2种不同金属材料的力学参数
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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